Efficacy and safety of a single intra-articular injection of 6 ml Hylan G-F 20 compared to placebo in Chinese patients with symptomatic knee osteoarthritis

Ke, Yan; Jiang, Wenxue; Xu, Yongsheng; Chen, Yajun; Zhang, Qingsong; Xue, Qingyun; Lin, Jianhao; Ngai, Wilson; Nian, Gaowei; Fazeli, Mir Sohail; Xie, Yao; Zhu, Zhenan

doi:10.1186/s12891-021-04252-2

Cited by 8 publications

(7 citation statements)

References 42 publications

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“…Of the 169 identified trials, 25 were large, placebo controlled trials ( table 1 ), 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 which randomised 9423 participants (mean age 62 years, 59% women, mean disease duration 5.2 years). Twenty four trials reported data for pain intensity (main analysis), 19 trials reported data for function, and 15 trials reported data for serious adverse events.…”

Section: Resultsmentioning

confidence: 99%

“…The median total trial follow-up was 24 weeks (8.6-27). The median average age of participants was 61 (58)(59)(60)(61)(62)(63)(64), whereas the median percentage of women was 62 (54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71). The clinical benefit of viscosupplementation was examined most frequently through open label trials as an add-on to standard treatment compared with standard treatment alone (93, 55%), followed by placebo controlled trials (76, 45%).…”

Section: Discussionmentioning

confidence: 99%

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Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis

Pereira

Jüni

Saadat

et al. 2022

BMJ

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Objective To evaluate the effectiveness and safety of viscosupplementation for pain and function in patients with knee osteoarthritis. Design Systematic review and meta-analysis of randomised trials. Data sources Searches were conducted of Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to 11 September 2021. Unpublished trials were identified from the grey literature and trial registries. Eligibility criteria for study selection Randomised trials comparing viscosupplementation with placebo or no intervention for knee osteoarthritis treatment. Main outcome measures The prespecified primary outcome was pain intensity. Secondary outcomes were function and serious adverse events. Pain and function were analysed as standardised mean differences (SMDs). The prespecified minimal clinically important between group difference was −0.37 SMD. Serious adverse events were analysed as relative risks. Methods Two reviewers independently extracted relevant data and assessed the risk of bias of trials using the Cochrane risk of bias tool. The predefined main analysis was based only on large, placebo controlled trials with ≥100 participants per group. Summary results were obtained through a random effects meta-analysis model. Cumulative meta-analysis and trial sequential analysis under a random effects model were also performed. Results 169 trials provided data on 21 163 randomised participants. Evidence of small study effects and publication biases was observed for pain and function (Egger’s tests with P<0.001 and asymmetric funnel plots). Twenty four large, placebo controlled trials (8997 randomised participants) included in the main analysis of pain indicated that viscosupplementation was associated with a small reduction in pain intensity compared with placebo (SMD −0.08, 95% confidence interval −0.15 to −0.02), with the lower bound of the 95% confidence interval excluding the minimal clinically important between group difference. This effect corresponds to a difference in pain scores of −2.0 mm (95% confidence interval −3.8 to −0.5 mm) on a 100 mm visual analogue scale. Trial sequential analysis for pain indicated that since 2009 there has been conclusive evidence of clinical equivalence between viscosupplementation and placebo. Similar conclusions were obtained for function. Based on 15 large, placebo controlled trials on 6462 randomised participants, viscosupplementation was associated with a statistically significant higher risk of serious adverse events than placebo (relative risk 1.49, 95% confidence interval 1.12 to 1.98). Conclusion Strong conclusive evidence indicates that viscosupplementation leads to a small reduction in knee osteoarthritis pain compared with placebo, but the difference is less than the minimal clinically important between group difference. Strong conclusive evidence indicates that viscosupplementation is also associated with an increased risk of serious adverse events compared with placebo. The findings do not support broad use of viscosupplementation for the treatment of knee osteoarthritis. Systematic review registration PROSPERO CRD42021236894.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis

Pereira

Jüni

Saadat

et al. 2022

BMJ

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“…Take, for example, two recent randomized, multicenter, quadruple-blinded, 26-week, placebo-controlled trials investigating the efficacy and safety of the same IA HA in adults with KOA, with nearly identical study designs apart from geographic location. 46 , 62 In the first trial, conducted in Europe, the primary efficacy endpoint of change in the Western Ontario and McMaster Univiersities Osteoarthritis Index (WOMAC) A from baseline to 26 weeks was significantly better for the active treatment compared with placebo (IA HA −0.84 versus IA saline −0.69; p = 0.047). 11 However, in the trial conducted in China, the primary efficacy endpoint of change in WOMAC A1 from baseline to 26 weeks between the IA HA and the placebo did not reach statistical significance (IA HA −2.146 versus IA saline −2.271; p = 0.36).…”

Section: Discussionmentioning

confidence: 99%

Intra-articular placebo effect in the treatment of knee osteoarthritis: a survey of the current clinical evidence

Fazeli¹,

McIntyre²,

Huang

et al. 2022

Therapeutic Advances in Musculoskeletal

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Knee osteoarthritis (KOA) is a debilitating disease characterized by chronic pain, stiffness, and decreased mobility. Intra-articular injectable therapies show good clinical efficacy in improving symptoms; however, these therapies and their comparators (intra-articular saline) have been associated with a large underlying placebo effect. We aimed to describe the existing evidence on the challenges, hypotheses, and potential solutions to mitigate the intra-articular placebo effect in clinical trials in KOA. A targeted literature review was conducted by searching Embase, MEDLINE®, and CENTRAL using predefined study selection criteria. All eligible studies identified were extracted for relevant data, and results were narratively summarized. Forty-three studies were included following screening. Challenges associated with the intra-articular placebo effect included its ability to mask the comparative efficacy of active treatments in trials ( n = 7 studies), long-lasting effects (up to 6 months; n = 3), and substantial variation of placebo effect sizes across populations ( n = 3). Hypotheses for the mechanism of the placebo effect included aspiration of synovial fluid during administration ( n = 6) and dilution of inflammatory mediators ( n = 2). Factors affecting the placebo effect size were more invasive routes of administration (e.g., injection versus oral; n = 4) and patient expectations ( n = 2). Proposed solutions included the suggestion for readers to weigh the relevance of clinical trial evidence against the presence of large underlying placebo effects ( n = 9), discontinuation of intra-articular saline as an appropriate placebo ( n = 5), and inclusion of ‘no treatment’ or sham injection as a control ( n = 4). The intra-articular placebo effect is a well-documented occurrence in KOA clinical trials, and it is suggested that it be accounted for when designing randomized controlled trials. Awareness and understanding of the intra-articular placebo effect in KOA are required for fair interpretation of clinical trial evidence.

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“…The control group received an established osteoarthritis product (Synvisc 0.8%, 2.0 ml). The positive effects and safety of Synvisc 0.8%, 2.0 ml have been tested in several studies (20)(21)(22)(23)(24)(25)(26).…”

Section: Control Groupmentioning

confidence: 99%

“…The sodium hyaluronate contained (hylan G-F 20) is a high molecular weight, cross-linked derivate of hyaluronan (Table 3). Unlike the sodium hyaluronate used in the comparison product INNORYOS 2.2%, Hylan G-F 20 is not of bacterial but of animal origin (rooster comb) (25).…”

Section: Control Groupmentioning

confidence: 99%

Effectiveness and safety of the hyaluronic acid INNORYOS 2.2% in patients with early to advanced knee osteoarthritis. A prospective non-interventional randomized clinical trial.

Hofweber,

von Stengel,

Nürnberger

et al. 2024

Preprint

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Introduction: We determined the effectiveness and safety of INNORYOS 2.2% hyaluronic acid (HA) containing 15mg of niacinamide on knee pain, stiffness and function in people with knee OA compared with an established agent. Further study objectives were to monitor side effects during the study period. Methods: The 26-week prospective non-interventional open clinical trial tested on non-inferiority of INNORYOS 2.2% compared to an established HA product (Synvisc 0.8%, 2.0 ml). Briefly, 90 people with knee OA (Kellgren-Lawrence grade I to III), 40–85 years old, were allocated randomly to the two groups. HA injections were carried out at baseline and after 1 and 2 weeks. ANCOVA that adjusted for baseline differences was applied to determine between group differences (i.e. “effects”) after 26 weeks. Results: None of the 90 participants (65.0 ± 10.5 years, BMI: 30.2 ± 5.5 kg/m2) quit the study or was lost to follow-up. In summary WOMAC pain score (p = .26) and function score (p = .49) did not differ significantly between the groups, but data significant better effect after INNORYOS 2.2% were observed for WOMAC stiffness subscale (p = .009). In detail, changes from baseline to 26-week FU average 43.6% (29.1%) for “pain”, 25.9% (0%) for “stiffness” and 37% (27.6%) for “function” subscale in the INNORYOS (Synvisc) group. No adverse effects were observed or reported by the participants. As determined by personal interviews and recorded in the questionnaires no changes of co-medication with impact on the study outcomes were observed. Conclusion: We did not determine significantly lower effects compared with the established product. In contrast, INNORYOS 2.2% tendentially revealed more favourable effect on all WOMAC categories (significant for “stiffness”). Thus, the present study provided further evidence for the effectiveness and safety of INNORYOS 2.2% in patients with early to advanced knee osteoarthritis.

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Efficacy and safety of a single intra-articular injection of 6 ml Hylan G-F 20 compared to placebo in Chinese patients with symptomatic knee osteoarthritis

Cited by 8 publications

References 42 publications

Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis

Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis

Intra-articular placebo effect in the treatment of knee osteoarthritis: a survey of the current clinical evidence

Effectiveness and safety of the hyaluronic acid INNORYOS 2.2% in patients with early to advanced knee osteoarthritis. A prospective non-interventional randomized clinical trial.

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